3846 Imminent fracture rates whilst on anabolic treatment for osteoporosis

Osteoporosis

Fragility fractures of the hip are known to be followed frequently by subsequent fragility fractures, including second hip fractures. Data on subsequent fractures are available for aggregated index femoral neck and intertrochanteric femoral fractures, grouped generically as hip fractures, but not specifically for femoral neck fractures. There is increasing recognition that a subsequent fracture often occurs early after a hip fracture in the elderly, creating an emphasis on the concept of "imminent fracture risk." Since 2000, there have been many reports on the care gap in interventions after a fragility fracture, with concern regarding the slow uptake of appropriate systemic treatments designed to prevent a subsequent fracture in high-risk patients. As planned a priori, we performed an analysis of subsequent fractures after an index femoral neck fracture in 2 prospective clinical trials involving 2,520 patients from 90 sites on 5 continents. We recorded the incidence and time of occurrence of all secondary fragility fractures as well as the reported use of bone-protective medication in all subjects. In the 24 months following the index femoral neck fracture, 226 (9.0%) of 2,520 patients sustained at least 1 subsequent fragility fracture, including 113 hip fractures (4.5%). The median interval from the index fracture to a subsequent fracture was approximately 9.0 months. Only 25.2% (634) of the 2,520 patients reported using bone-protective medications at any time during follow-up. Female patients, those with nondisplaced index fractures, and those treated with arthroplasty, were more likely to have received protective medication. Subsequent fractures, including second hip fractures, occurred frequently and early following an index femoral neck fracture in 2 large global cohorts. Interventions to prevent a subsequent fracture were instituted in only 1 of 4 patients, even though a focused directive was included in both study protocols. Prognostic Level II . See Instructions for Authors for a complete description of levels of evidence.

The clinical significance of osteoporosis is in the occurrence of fractures and re-fractures. The main risk factor of sustaining a fracture is a previous one, but a recent fracture is a better fracture risk factor than fracture history. The role of the recency of fracture has been shown for both vertebral and non-vertebral fracture risk. This imminent risk is explained by both bone-related factors (underlying osteoporosis) and fall-related factors (including those related to postfracture care). Such a short-term increased risk has been shown also in patients initiating corticosteroids and in frail osteoporotic subjects with central nervous system (CNS) diseases or drugs targeting CNS, and thus a high risk of falls. Patients with an imminent (i.e. 2years) risk of fracture or refracture should be identified in priority in order to receive an immediate treatment and a program of fall prevention.

Romosozumab is an anabolic agent approved for the treatment of severe osteoporosis in postmenopausal women and in men at high risk of fracture. However, real-world data on its effectiveness, particularly in patients with diabetes mellitus (DM) or prior exposure to antiresorptive therapy, remain limited. Adult patients (⩾18 years) who received romosozumab between January 2021 and May 2024 and had both baseline and post-treatment dual-energy X-ray absorptiometry (DEXA) scans were included. Bone mineral density (BMD) at the lumbar spine, total hip and femoral neck was assessed before and after 12 months of therapy. Subgroup analyses were undertaken according to diabetes status and previous antiresorptive therapy exposure. Eighty-seven patients were included (mean age 66.7 ± 13.0 years; 94.3% female). The median percentage increase in lumbar spine BMD was 6.7% (IQR 1.3-12.6), while increases at the total hip and femoral neck were 2.9% (IQR -1.1 to 9.1) and 2.3% (IQR -3.9 to 9.7), respectively. Patients without diabetes demonstrated significantly greater BMD gains than those with diabetes at the lumbar spine (9.9% vs 3.1%; P = .020), total hip (4.1% vs 0.3%; P = .027), and femoral neck (3.9% vs 0.1%; P = .028). Similarly, treatment-naïve patients had greater improvements in total hip BMD compared with those with prior antiresorptive exposure (8.3% vs 2.2%; P = .004). Romosozumab significantly increased BMD at the lumbar spine, total hip and femoral neck after 12 months of treatment. The response was more pronounced in patients without diabetes and those who were treatment-naïve, suggesting that metabolic status and previous antiresorptive therapy may influence treatment effectiveness. Prospective studies are warranted to evaluate long-term fracture outcomes and the durability of these effects.

Kidney transplant recipients face a high risk of adverse events, including fractures. Reported fracture rates post-transplant vary widely and may have changed over time. The consequences of a fracture, especially subsequent fractures, remain under-investigated. This study examined the risk and prognosis of fractures after kidney transplantation in the current era. This retrospective cohort study included all adults who received a first single-organ kidney transplant between 2000 and 2022 in Denmark. Nationwide healthcare registries were utilized to identify the study population and provide demographic data, diagnostic and procedural codes, and prescription data. Cumulative incidence (risk) of both first fracture and subsequent fracture was computed, treating death as a competing risk. Crude, and sex- and age-standardized incidence rates were estimated for different time periods. The study included 3977 first kidney transplant recipients, of whom 788 sustained any post-transplant fracture. The 10-year risk of fracture was 21% (95% confidence interval 20-23). Crude incidence rates of any fracture remained unchanged over time, while standardized estimates showed a slight decline. Fractures were primarily located at the peripheral skeleton. Twenty-eight percent of patients with a fracture sustained a subsequent fracture, with the highest incidence at 6-12 months following the first event. Kidney transplant recipients remain at high fracture risk, with unchanged fracture rates over the past 20 years. The imminent fracture risk following a first fracture is high and largely unaddressed. Although formal guidelines have yet to be established, this knowledge should urge clinicians to perform risk assessment and consider intervention following a post-transplant fracture.

Fragility fractures constitute a major public health problem worldwide, causing important high morbidity and mortality rates. The aim was to present the epidemiology of fragility fractures and to assess the imminent risk of a subsequent fracture and mortality. This is a retrospective population-based cohort study (n = 1369) with a fragility fracture. We estimated the incidence rate of index fragility fractures and obtained information on the subsequent fractures and death during a follow-up of up to three years. We assessed the effect of age, sex, and skeletal site of index fracture as independent risk factors of further fractures and mortality. Incidence rate of index fragility fractures was 86.9/10,000 person-years, with highest rates for hip fractures in women aged ≥80 years. The risk of fracture was higher in subjects with a recent fracture (Relative Risk(RR), 1.80; p < 0.01). Higher age was an independent risk factor for further fracture events. Significant excess mortality was found in subjects aged ≥80 years and with a previous hip fracture (hazard ratio, 3.43 and 2.48, respectively). It is the first study in Spain to evaluate the incidence of major osteoporotic fractures, not only of the hip, and the rate of imminent fracture. Our results provide further evidence highlighting the need for early treatment.

BackgroundThe secondary fracture prevention gap in the osteoporosis field has been previously described as a ‘crisis’. Closing this gap is increasingly important in the context of accumulating evidence showing that an incident fragility fracture is associated with an increased risk of subsequent fracture within 1–2 years, known as imminent fracture risk. The objective of this study was to use health services data to characterize the time between index fragility fractures occurring at different osteoporotic sites and subsequent fractures.MethodsThis retrospective observational study used de-identified health services data from the publicly funded healthcare system in Ontario, the largest province of Canada. Patients aged > 65 with an index fragility fracture occurring between 2011 and 2015 were identified from the ICES Data Repository using International Classification of Diseases (ICD)-10 codes. We examined median time to subsequent fragility fractures for osteoporotic fracture sites until the end of follow-up (2017). BMD assessment and use of osteoporosis therapies following index fracture were also characterized.ResultsAmong 115,776 patients with an index fragility fracture, 17.8% incurred a second fragility fracture. Median time between index and second fracture occurring at any site was 555 days (interquartile range: 236–955). For each index fracture site examined, median time from index to second fracture was < 2 years. The proportion of patients with BMD assessment was 10.3% ≤1 year prior to and 16.4% ≤1 year post index fracture. The proportion of patients receiving osteoporosis therapy was 29.8% ≤1 year prior, 34.6% ≤1 year post, and 25.9% > 3 years post index fracture.ConclusionsThis cohort of Canadian patients aged > 65 years who experienced a fragility fracture at any site are at imminent risk of experiencing subsequent fracture within the next 2 years and should be proactively assessed and treated.

A 60 year old female was under long-term follow-up for rheumatoid arthritis, for which she took methotrexate. Ten years previously she had been found to have a single vertebral fracture and her fracture risk, assessed using The WHO Fracture Risk Assessment Tool (FRAX®), was calculated as a 13% risk of major osteoporotic fracture over the next 10 years. According to The National Osteoporosis Guideline Group (NOGG) recommendations, she underwent Dual X-ray Absorptiometry (DXA) which demonstrated a bone mineral density T-score of -1.7 at the femoral neck. Lifestyle, vitamin D and calcium intake were optimised and follow-up was arranged for 6 months. Prior to her next appointment she fell and sustained a fracture of the distal radius. On fracture liaison review her FRAX® risk of fracture was 14% (rising due to an increased year of age) despite the recent change in clinical circumstances. This case serves to emphasise the clinical conundra associated with imminent fracture risk (the 2 years after a fracture when the patient is at a significantly higher risk of fracture) and the difficulties with the decision to treat. Disclosure of Interests: None declared

SAT0452 DIFFERENT PROFILE OF RISK OF FRACTURE IN PATIENTS TREATED WITH ANTI-OSTEOPOROTIC DRUGS IN ITALY USING A NEW ALGORITHM

With global population growth and advancing age, fragility fractures present a major healthcare challenge that current approaches have not resolved. Although pharmacological agents have been shown to reduce fragility fracture risk, there remain unmet needs in clinical care, especially for patients at imminent risk of hip fracture, given the delay between treatment initiation and observed protective effect. This gap suggests a need for novel approaches, including hip procedures that strengthen bone locally and quickly. The purpose of this report is to describe a procedural technique that has been shown in ex vivo and clinical studies to rapidly enhance proximal femur biomechanical properties and leads to new bone formation. Local osteo-enhancement procedure (LOEP) is a minimally invasive surgical procedure to address bone voids in the pelvis and extremities, including in the proximal femur, due to trauma and disease such as osteoporosis. After surgical preparation of voids within the femoral neck and intertrochanteric regions of the proximal femur, a resorbable, triphasic, calcium-based implant material, AGN1, is delivered to that site. Clinical studies demonstrate consistent implant material resorption, concurrent replacement of the material with bone, and a significant, durable increase in areal bone mineral density (aBMD). The procedural technique has been studied as a standalone procedure and as concomitant surgery taking place in the same operative session as the surgical treatment of a contralateral index hip fragility fracture. In the study of concomitant use, LOEP was reported not to disrupt the standard of care for mobilization and rehabilitation for hip fracture. The clinical studies completed suggest that the procedure demonstrates an acceptable safety profile and has the potential to reduce the incidence of hip fragility fractures.

Bone microarchitecture measured at the iliac crest at 6 mo was confirmed to be a reasonable surrogate for, and a predictor of, architecture and strength of the femoral neck and lumbar vertebra after 18 mo of teriparatide treatment. However, the data taken together showed the importance of cortical bone volume for vertebra to assess pharmacological effects on bone quality. Improvements in bone architecture with teriparatide treatment are suggested to contribute to fracture risk reduction in osteoporotic patients. Teriparatide significantly improves microarchitecture in the iliac crest of humans by stimulating bone modeling and remodeling processes that differ dramatically from those induced by antiresorptives. The relationship between improvements of bone microarchitecture and improvements of bone strength with teriparatide treatment has not yet been fully studied. Ovariectomized monkeys were administered vehicle (n = 20); teriparatide 1.0 microg/kg/d (n = 19); or teriparatide 5.0 microg/kg/d (n = 21) for 18 mo. Iliac crest biopsies were obtained at 6 and 15 mo after initiation of treatment. Animals were killed after 18 mo of treatment, and adjacent vertebrae or contralateral proximal femora were processed for biomechanical or histomorphometric analyses. Pearson correlation analyses were performed to assess the relationship between biomechanical and static histomorphometric parameters of lumbar vertebra, femoral neck, and iliac crest biopsies. Static histomorphometric parameters of the 6- and 15-mo biopsies were significantly correlated with the vertebral and femoral neck parameters obtained at 18 mo of teriparatide treatment. Iliac crest biopsy parameters at 6 and 15 mo also correlated with vertebral and femoral neck strength at 18 mo. Static histomorphometry of the lumbar vertebra and femoral neck at 18 mo also significantly correlated with strength at these sites. However, cortical bone volume of the lumbar vertebrae had the strongest correlation with vertebral and femoral neck strength (r = 0.74 and 0.71, respectively). Teriparatide dose dependently improved cortical and trabecular microarchitecture of vertebra and femoral neck, as well as trabecular microarchitecture of the iliac crest. Bone microarchitecture at all sites was significantly correlated with lumbar vertebra and femoral neck strength. Cortical bone volume of vertebra had the strongest correlation with vertebral and femoral neck strength. Therefore, structural improvement seemed to be part of the mechanism for improved strength observed with teriparatide treatment. Trabecular bone architecture of the iliac crest at 6 mo also correlated with vertebral and femoral neck strength, as did femoral neck (cortical and trabecular) histomorphometry and trabecular histomorphometry of vertebra after 18 mo of treatment. Because clinical assessment of cortical bone volume is not readily possible for vertebra noninvasively, these findings confirm the importance of iliac crest biopsies to monitor skeletal health and show that biopsies are a reasonable surrogate to assess spine and femoral neck structure and function.

We assessed the clinical usefulness of bone density measurements at the os calcis as a screening tool to identify patients with low bone density at the lumbar spine and femoral neck. Bone mineral density (BMD) was recorded in 443 women (mean age 60 years) referred to a bone densitometry service. Measurements were made at the lumbar spine and femoral neck using a Lunar DPXL and at the right os calcis using a Peripheral Instantaneous X-ray Imaging (PIXI) dual-energy X-ray absorptiometry system. Average T-scores derived using the manufacturer's data were: 1.59 for the lumbar spine, -1.41 for the femoral neck and -0.87 for the os calcis. The prevalence of osteoporosis using WHO criteria (T-scores of -2.5 or less) was 36% for the lumbar spine or femoral neck but only 9.7% for the os calcis. BMD of the os calcis correlated with that at the lumbar spine (r = 0.69, p < 0.001) and femoral neck (r = 0.67, p < 0.001). The area under the receiver operator characteristics curve was 0.836 (standard error 0.020) for the os calcis related to osteoporosis at the lumbar spine or femoral neck. Optimal accuracy was obtained at a T-score of < or = -1.3 (BMD 0.39 g/cm2) when the sensitivity was 69.6% (95% confidence interval 65.3, 73.9%) and specificity 82.6% (95% confidence interval 79.1, 86.1%). However, the probability of diagnosing low bone density from a given BMD at the os calcis varied by age and site scanned. Accordingly, for informing management strategies, the choice of a single cutoff BMD at the os calcis may not be appropriate and several thresholds may be adopted based on age, the site of interest (lumbar spine or femoral neck) and consideration of associated clinical features. Thus, the use of heel bone density scanners could reduce the number of axial bone density measurements required. The advantages of portability, low cost and shorter scan times should reduce the cost of detection and provide a greater opportunity for identification of women at risk of fracture.

Outcome of very high-risk patients treated by Sotrovimab for mild-to-moderate COVID-19 Omicron, a prospective cohort study (the ANRS 0003S COCOPREV study)

Managing osteoporotic patients suboptimally adherent to bisphosphonates (BPs) is difficult. Such patients who remained at higher risk for fracture (≥1 risk factor) were transitioned to denosumab or a monthly oral BP. Denosumab-treated subjects had significantly greater increases in bone mineral density and decreases in bone turnover in this 12-month study. A clinical need exists to manage patients who are suboptimally adherent to oral BPs and remain at higher risk for fracture. Here, we compare the effects on bone mineral density (BMD) and bone turnover of transitioning such patients to denosumab or monthly oral BP (ibandronate or risedronate). In two previous multicenter, open-label studies, postmenopausal women ≥55years previously treated with, though suboptimally adherent to, a daily or weekly BP were randomized to denosumab 60mg subcutaneously every 6months (N = 852) or oral BP 150mg monthly (N = 851) for 12months. In this combined post-hoc analysis, a subset of higher risk subjects was identified, and the percentage changes from baseline in BMD and serum C-telopeptide of type I collagen (sCTX-1) were assessed. In the overall population, denosumab was associated with greater gains in BMD at 12months than monthly oral BP at the total hip, femoral neck, and lumbar spine (p < 0.0001 for all). In higher risk subjects, denosumab led to greater gains in BMD than oral BPs at the total hip (2.2 vs 0.8%), femoral neck (1.8 vs 0.3%), and lumbar spine (3.7 vs 1.4%) (p < 0.0001 for all). Denosumab also led to greater decreases in sCTX-1 in the overall population and higher risk subjects at months 1 and 6 (p < 0.0001 for both). Adverse events and serious adverse events were generally similar between treatment groups. Transitioning to denosumab was well tolerated and more effective in increasing BMD and reducing bone turnover than cycling to a monthly oral BP treatment in subjects who remained at higher fracture risk despite suboptimal BP treatment.

Early diagnosis of osteoporosis and estimation of subjects that are at high risk for fracture, is neccesary for osteoporosis treatment. Dual-energy X-ray absorptometry (DXA) is a modern method for bone mineral density (BMD) evaluation. However, along BMD, clinical risk factors may significantly influence fracture development. Therefore, FRAX algorithm was designed for the assessment of a ten-year risk for serious osteoporotic fractures (SOF), as well as hip fractures. In the current study, we tried to evaluate the possible lumbal spine and hip BMD influence on ten year risk for SOF and hip fractures and potential role of FRAX in predicting the therapy in postmenopausal women with osteopenia. We performed the study on 385 postmenopausal women. According to the DXA measurements, at the lumbal (L) spine (L1–L4) and hip (femor neck), patients were then classified as normal, osteopenic, or osteoporotic. BMD evaluation included the L spine and the hip (subgroup 1), and only on the L spine (subgroup 2). By filling up the FRAX questionnaire, a ten-year risk for SOF fracture and hip fracture was calculated. BMD evaluation, in complete patient’s group and in subgroup 1, resulted in the highest number of osteoporosis (61.04%, 48.08%, retrospectively), while ospeopenia was a main finding in subgroup 2. In the subgroup 1, a high risk for SOF and hip fracture was detected in 16.45% and with high risk for hip fracture in 11.38% subjects. In subgroup 2, only high risk for hip fracture was observed in 3.16% subjects, indicating the active medicament treatment. Simultaneously, correlation of BMD results with FRAX values for SOF and hip fracture, showed significant negative correlation (p&lt;0.001). Obtained results showed significant role of femur neck BMD evaluation in predicting the future factors, which may, together with FRAX analysis, improve the therapy approach in postmenopausal women with ospeopenia.